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Born at Rumigny, he attended school in Mantes-sur-Seine (now Mantes-la-Jolie). Afterwards, he studied rhetoric and philosophy at the Collège de Lisieux and then theology at the Collège de Navarre. He was left destitute in 1731 by the death of his father, who had held a post in the household of the duchess of Vendôme. However, he was supported in his studies by the Duc de Bourbon, his father's former patron.[3]

After he graduated, he did not accept ordination as a priest but took deacon's orders, becoming an Abbé. He concentrated thereafter on science, and, through the patronage of Jacques Cassini, obtained employment, first in surveying the coast from Nantes to Bayonne, then, in 1739, in remeasuring the French meridian arc, for which he is honored with a pyramid at Juvisy-sur-Orge. The success of this difficult operation, which occupied two years, and achieved the correction of the anomalous result published by Jacques Cassini in 1718, was mainly due to Lacaille's industry and skill. He was rewarded by admission to the Royal Academy of Sciences and appointment as Professor of mathematics in the Mazarin college of the University of Paris, where he constructed a small observatory fitted for his own use. He was the author of a number of influential textbooks and a firm advocate of Newtonian gravitational theory. His students included Antoine Lavoisier and Jean Sylvain Bailly, both of whom were later guillotined during the Revolution.

A memorial to the Abbé de Lacaille and Thomas Maclear, at Aurora in the Western Cape of South Africa. The English portion of the inscription reads: "This is the site of the Maclear Beacon positioned in 1838 near the original North Terminal of the Arc of Meridian positioned by Abbé de Lacaille, the first surveyor to introduce Geodetic Surveying into South Africa." Open the image to see the Afrikaans portion.

His desire to determine the distances of the planets trigonometrically, using the longest possible baseline, led him to propose, in 1750, an expedition to the Cape of Good Hope. This was officially sanctioned by Roland-Michel Barrin de La Galissonière. There, he constructed an observatory on the shore of Table Bay with the support of the Dutch Governor Ryk Tulbagh. The primary result of his two-year stay was observed nearly 10,000 southern stars, the production of which required observing every night for over a year. In the course of his survey he took note of 42 nebulous objects. He also achieved his aim of determining the lunar and solar parallaxes (Mars serving as an intermediary). This work required near-simultaneous observations from Europe which were carried out by Jérôme Lalande.

His southern catalogue, called Coelum Australe Stelliferum, was published posthumously in 1763. He found it necessary to introduce 14 new constellations which have since become standard.[4] One of these was Mons Mensae, the only constellation named after a terrestrial feature (the Table Mountain).

During his voyage to the southern hemisphere as a passenger on the vessel Le Glorieux, captained by the noted hydrographer Jean-Baptiste d'Après de Mannevillette, Lacaille became conscious of the difficulties in determining positions at sea. On his return to Paris he prepared the first set of tables of the Moon's position that was accurate enough to use for determining time and longitude by the method of 'Lunars' (Lunar distances) using the orbital theory of Clairaut. Lacaille was in fact an indefatigable calculator. Apart from constructing astronomical ephemerides and mathematical tables, he calculated a table of eclipses for 1800 years. Lalande said of him that, during a comparatively short life, he had made more observations and calculations than all the astronomers of his time put together. The quality of his work rivalled its quantity, while the disinterestedness and rectitude of his moral character earned him universal respect.

On his return to Paris in 1754, following a diversion to Mauritius, Lacaille was distressed to find himself an object of public attention. He resumed his work at the Mazarin College.

In 1757 he published his Astronomiae Fundamenta Novissimus, containing a list of about 400 bright stars with positions corrected for aberration and nutation. He carried out calculations on comet orbits and was responsible for giving Halley's Comet its name. His last public lecture, given on 14 September 1761 at the Royal Academy of Sciences, summarised the improvements to astronomy that had occurred during his lifetime, to which he had made no small contribution.
His death, probably caused in part by over-work, occurred in 1762. He was buried in the vaults of the Mazarin College, now the Institut de France in Paris.

Calculations by him of eclipses for eighteen hundred years were inserted in L'Art de vérifier les dates by Benedictine historian Charles Clémencet (1750)

He communicated to the Academy in 1755 a classed catalogue of forty two southern nebulae,[10] and gave in t. ii. of his Ephémérides (1755) practical rules for the employment of the lunar method of longitudes, proposing in his additions to Pierre Bouguer's Traité de Navigation (1760) the model of a nautical almanac.

A catalogue of 9766 stars in the southern hemisphere,for the beginning of the year 1750: from the observations of the Abbé de Lacaille, made at the cap of Good Hope in the years 1751 and 1752; with a preface by Sir J. F. W. Herschel (1847), giving zone observations of about 10,000 stars, re-edited by F. Baily

^The traditional birth date of 15 March 1713 has been questioned due to many infants of the Catholic Church being baptised on the day of their birth in the 17th and 18th centuries. Thomas Hockey et al.: The Biographical Dictionary of Astronomers, Springer, 2007, ISBN978-0-387-31022-0, p665; and his baptism date is 15 December 1713; babies were normally baptised on the day that they were born. Boquet, F. (1913). "Le Bicentenaire de Lacaille". L'Astronomie. 27: 457–473. Bibcode:1913LAstr..27..457B.. see page 459